A distorted pupil could be caused by an iris melanoma.

Melanoma isolated to the iris is rare and can present with a distorted pupil. This is a case report of an 81-year-old asymptomatic man, who had a large pigmented element in his left iris through 30 years. Because of involvement of the angle the tumour was excised with the ciliary body, and histopathologic examination revealed an iris melanoma. The aim of this report is to underscore the clinical signs of an iris melanoma and when surgery is needed.

Peripheral refraction, relative peripheral refraction, and axial growth: 18-month data from the randomised study-Clinical study Of Near-sightedness; TReatment with Orthokeratology Lenses (CONTROL study).

PURPOSE: To investigate changes in peripheral and relative peripheral refraction (RPR) during orthokeratology lens (OKL) use in children, and predictors for myopia progression in a randomized controlled trial. METHODS: Refraction and axial length (AL) were measured at baseline, 6, 12, and 18 months for children aged 6-12 years, with myopia of 0.5 to 4.75 dioptres (D) spherical component randomized to either OKL or single-vision spectacles (SVS) at baseline. Cycloplegic spherical equivalent refractive error (SEQ) was measured on-axis and eccentric at 10°, 20°, and 30° during nasal and temporal gaze in the horizontal plane with Shin-Nippon Nvision-K 5001. RPR was computed as SEQ(eccentricity) minus SEQ(on axis) . AL was measured with Lenstar LS900. RESULTS: Twenty-one and 28 subjects from the OKL and SVS groups, respectively were available for analysis. OKL wear induced significant myopic RPR at all eccentricities (p ≤ 0.004) whereas peripheral refraction only changed in two out of six eccentric measuring points. Baseline peripheral refraction SEQ at all eccentricities, baseline on-axis SEQ, and baseline RPR at 30° nasal eccentricity were positively correlated to treatment efficacy defined as change in AL. CONCLUSION: We found no correlations between change in RPR and treatment efficacy defined as change in AL. Interestingly, our results suggest that the central emmetropisation that occurs during OKL-use accounts for most of the optical changes and to a lesser extent the mid-peripheral plus-zone of the lens.

Radiological identification of the globus pallidus motor subregion in Parkinson's disease.

OBJECTIVE: Globus pallidus (GP) lesioning improves motor symptoms of Parkinson's disease (PD) and is occasionally associated with nonmotor side effects. Although these variable clinical effects were shown to be site-specific within the GP, the motor and nonmotor subregions have not been distinguished radiologically in patients with PD. The GP was recently found to have a distinct radiological signature on diffusion MRI (dMRI), potentially related to its unique cellular content and organization (or tissue architecture). In this study, the authors hypothesize that the magnitude of water diffusivity, a surrogate for tissue architecture, will radiologically distinguish motor from nonmotor GP subregions in patients with PD. They also hypothesize that the therapeutic focused ultrasound pallidotomy lesions will preferentially overlap the motor subregion. METHODS: Diffusion MRI from healthy subjects (n = 45, test-retest S1200 cohort) and PD patients (n = 33) was parcellated based on the magnitude of water diffusivity in the GP, as measured orientation distribution function (ODF). A clustering algorithm was used to identify GP parcels with distinct ODF magnitude. The individual parcels were used as seeds for tractography to distinguish motor from nonmotor subregions. The locations of focused ultrasound lesions relative to the GP parcels were also analyzed in 11 patients with PD. RESULTS: Radiologically, three distinct parcels were identified within the GP in healthy controls and PD patients: posterior, central, and anterior. The posterior and central parcels comprised the motor subregion and the anterior parcel was classified as a nonmotor subregion based on their tractography connections. The focused ultrasound lesions preferentially overlapped with the motor subregion (posterior more than central). The hotspots for motor improvement were localized in the posterior GP parcel. CONCLUSIONS: Using a data-driven approach of ODF-based parcellation, the authors radiologically distinguished GP motor subregions in patients with PD. This method can aid stereotactic targeting in patients with PD undergoing surgical treatments, especially focused ultrasound ablation.

The association of nadir CD4-T cell count and endothelial dysfunction in a healthy HIV cohort without major cardiovascular risk factors.

OBJECTIVES: HIV-infected population may have increased risk of cardiovascular disease. The prevalence of traditional cardiovascular disease risk factors such as hypertension, diabetes and dyslipidemia in HIV-infected individuals has made it difficult to assess the direct effects of HIV and immune factors on endothelial dysfunction and associated increased risk of atherosclerosis. The purpose of this study was to investigate indicators of endothelial dysfunction in an HIV cohort without hypertension and diabetes. METHODS: We studied 19 HIV-infected patients between the ages of 25-76 years old with effectively suppressed viral load and without diagnosis of hypertension or diabetes. Endothelial function was measured by digital thermal monitoring of vascular reactivity using the VENDYS technique. Endothelial function was reported as vascular reactivity index. Systolic blood pressure and diastolic blood pressure at the time of VENDYS test were measured and latest lipid panels were recorded. The association between vascular reactivity index and CD4-T cells count, different antiretroviral therapy types (non-nucleoside reverse transcriptase, nucleoside reverse transcriptase, protease inhibitors, integrase inhibitors), vitamins use, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol was investigated. RESULTS: Mean vascular reactivity index was 1.87 ± 0.53. Vascular reactivity index, marker of endothelial dysfunction, showed a significant correlation with lower nadir CD4 count (p = 0.003) as well as low-density lipoprotein cholesterol (p = 0.02). No additional significant correlation between vascular reactivity index and the rest of the investigated variables was found. CONCLUSION: Vascular reactivity index, a clinical predictor of endothelial dysfunction, is associated with lower nadir CD4-T cell and low-density lipoprotein cholesterol in HIV-infected men with no history of hypertension or diabetes and before clinical evidence of cardiovascular disease.

Variations in keratometric values (K-value) after administration of three different eye drops - effects on the intraocular lens calculations in relation to cataract surgery.

PURPOSE: To investigate the variance in keratometric (K) values after administration of different eye drops (three tested), and the effects on intraocular lens (IOL) power calculations in relation to standard cataract surgery. METHODS: A prospective intervention study (pilot study) on 38 participants (22 women, 16 men, 58-88 years) undergoing 57 cataract surgeries. Three keratometries on each eye were performed: a baseline ('standard') keratometry about 9 weeks preoperatively, and two on the operation day; a 'dry'-measurement before interventions and a 'wet'-measurement after applying one of three eye drops (saline, Systane Ultra® , or Systane Complete® ). All standard cataract operations were uneventful. Variabilities in K-values, spherical equivalents (SEQs) for IOL power calculations (Barrett TK Universal II) and subjective manifest refractions (SRs) 6 weeks postoperatively were compared between groups. RESULTS: The 'wet' K-values had a similar variability to those of the 'standard' and 'dry' K-values (p > 0.05, anova on ranks). The mean paired differences in K-measurements between groups ranged within a small interval from -0.0107 to 0.0096 mm. After comparing the SEQ predictions with SR-measurements, the most precise IOL calculation was achieved after administration of a saline eye drop, but the precision was not statistically improved compared to the other drop modalities. CONCLUSION: The variability in K-values was not significantly changed by administration of any of the different eye drops tested, suggesting that artificial eye drops do not impact the keratometry or IOL power prediction.

Distinguishing Brain Impact of Aging and HIV Severity in Chronic HIV Using Multiparametric MR Imaging and MR Spectroscopy.

BACKGROUND: Combination antiretroviral therapy (cART) has transformed HIV into a manageable but complex chronic disease, in which it is uncertain which brain insults may relate to age vs initial disease severity. We evaluate N-acetyl-aspartate/creatine (NAA/Cr), white matter hyperintensities (WMH), and mean cortical thickness to identify which subclinical markers of brain insult best relate to CD4 nadir and aging. This is a prospective study of the association between brain markers with age and initial infection severity, based on CD4 nadir, in chronic HIV patients. METHODS: Thirty-seven chronic HIV patients (age 25-77 years) with successful viral suppression were scanned on a GE 3T magnetic resonance imaging scanner to obtain NAA/Cr (standardized and averaged over 5 brain regions), log-transformed WMH volume, and mean cortical thickness. The brain measures were fitted with both CD4 nadir and age to evaluate the significance of their relationship. RESULTS: NAA/Cr, WMH, and cortical thickness were all correlated with age and CD4 nadir in unadjusted associations. Stepwise regression models showed that NAA/Cr alone best predicted CD4 nadir (ß = 40.1 ± 13.3; P = .005), whereas WMH (ß = 2.3 ± .9; P = .02) and mean cortical thickness (ß = -2.7 ± 6.6; P < .0001) together produced the best model fit with age. NAA/Cr was higher for HIV stage 1 (CD4 nadir ≥ 500 cells/ µL; n = 15) compared with stage 2 (200 ≥ CD4 nadir < 500; n = 13) and stage 3 (CD4 nadir < 200; n = 9; P < .01 for both). CONCLUSIONS: In patients with effectively suppressed HIV, NAA reflects the subclinical brain impact of initial disease severity related to development of even mild immune compromise, whereas cortical thickness and WMH volume are useful to evaluate age-related changes.

Hyperfine-Structure-Induced Depolarization of Impulsively Aligned I_{2} Molecules.

A moderately intense 450 fs laser pulse is used to create rotational wave packets in gas phase I_{2} molecules. The ensuing time-dependent alignment, measured by Coulomb explosion imaging with a delayed probe pulse, exhibits the characteristic revival structures expected for rotational wave packets but also a complex nonperiodic substructure and decreasing mean alignment not observed before. A quantum mechanical model attributes the phenomena to coupling between the rotational angular momenta and the nuclear spins through the electric quadrupole interaction. The calculated alignment trace agrees very well with the experimental results.

Rotational dissociation of impulsively aligned van der Waals complexes.

The nonadiabatic alignment dynamics of weakly bound molecule-atom complexes, induced by a moderately intense 300 fs nonresonant laser pulse, is calculated by direct numerical solution of the time-dependent Schrödinger equation. Our method propagates the wave function according to the coupled channel equations for the complex, which can be done in a very efficient and stable manner out to large times. We present results for two van der Waal complexes, CS2-He and HCCH-He, as respective examples of linear molecules with large and small moments of inertia. Our main result is that at intensities typical of nonadiabatic alignment experiments, these complexes rapidly dissociate. In the case of the CS2-He complex, the ensuing rotational dynamics resembles that of isolated molecules, whereas for the HCCH-He complex, the detachment of the He atom severely perturbs and essentially quenches the subsequent rotational motion. At intensities of the laser pulse ≲2.0 × 1012 W/cm2, it is shown that the molecule-He complex can rotate and align without breaking apart. We discuss the implications of our findings for recent experiments on iodine molecules solvated in helium nanodroplets.

Strongly aligned molecules inside helium droplets in the near-adiabatic regime.

Iodine (I2) molecules embedded in He nanodroplets are aligned by a 160 ps long laser pulse. The highest degree of alignment, occurring at the peak of the pulse and quantified by ⟨cos2𝜃2D⟩, is measured as a function of the laser intensity. The results are well described by ⟨cos2𝜃2D⟩ calculated for a gas of isolated molecules each with an effective rotational constant of 0.6 times the gas-phase value and at a temperature of 0.4 K. Theoretical analysis using the angulon quasiparticle to describe rotating molecules in superfluid helium rationalizes why the alignment mechanism is similar to that of isolated molecules with an effective rotational constant. A major advantage of molecules in He droplets is that their 0.4 K temperature leads to stronger alignment than what can generally be achieved for gas phase molecules-here demonstrated by a direct comparison of the droplet results to measurements on a ∼1 K supersonic beam of isolated molecules. This point is further illustrated for a more complex system by measurements on 1,4-diiodobenzene and 1,4-dibromobenzene. For all three molecular species studied, the highest values of ⟨cos2𝜃2D⟩ achieved in He droplets exceed 0.96.

Nonadiabatic laser-induced alignment of molecules: Reconstructing ⟨𝖼𝗈𝗌𝟤 θ⟩ directly from ⟨𝖼𝗈𝗌𝟤 θ2D⟩ by Fourier analysis.

We present an efficient, noise-robust method based on Fourier analysis for reconstructing the three-dimensional measure of the alignment degree, ⟨cos2θ⟩, directly from its two-dimensional counterpart, ⟨cos2θ2D⟩. The method applies to nonadiabatic alignment of linear molecules induced by a linearly polarized, nonresonant laser pulse. Our theoretical analysis shows that the Fourier transform of the time-dependent ⟨cos2θ2D⟩ trace over one molecular rotational period contains additional frequency components compared to the Fourier transform of ⟨cos2θ⟩. These additional frequency components can be identified and removed from the Fourier spectrum of ⟨cos2θ2D⟩. By rescaling of the remaining frequency components, the Fourier spectrum of ⟨cos2θ⟩ is obtained and, finally, ⟨cos2θ⟩ is reconstructed through inverse Fourier transformation. The method allows the reconstruction of the ⟨cos2θ⟩ trace from a measured ⟨cos2θ2D⟩ trace, which is the typical observable of many experiments, and thereby provides direct comparison to calculated ⟨cos2θ⟩ traces, which is the commonly used alignment metric in theoretical descriptions. We illustrate our method by applying it to the measurement of nonadiabatic alignment of I2 molecules. In addition, we present an efficient algorithm for calculating the matrix elements of cos2θ2D and any other observable in the symmetric top basis. These matrix elements are required in the rescaling step, and they allow for highly efficient numerical calculation of ⟨cos2θ2D⟩ and ⟨cos2θ⟩ in general.

Laser-Induced Rotation of Iodine Molecules in Helium Nanodroplets: Revivals and Breaking Free.

Rotation of molecules embedded in helium nanodroplets is explored by a combination of fs laser-induced alignment experiments and angulon quasiparticle theory. We demonstrate that at low fluence of the fs alignment pulse, the molecule and its solvation shell can be set into coherent collective rotation lasting long enough to form revivals. With increasing fluence, however, the revivals disappear-instead, rotational dynamics as rapid as for an isolated molecule is observed during the first few picoseconds. Classical calculations trace this phenomenon to transient decoupling of the molecule from its helium shell. Our results open novel opportunities for studying nonequilibrium solute-solvent dynamics and quantum thermalization.

Corneal resistance to shear force after UVA-riboflavin cross-linking.

PURPOSE: We evaluated whether UVA-riboflavin collagen cross-linking (CXL) increases transverse stromal shear moduli ex vivo, whether the shear moduli are greater in the anterior compared to the posterior stroma, and whether the shear moduli are affected by CXL. METHODS: The resistance to unidirectional transverse shear of human (n = 18) and porcine (n = 42) corneas was measured in a custom engineered biaxial biomechanical setup at different hydrations. The corneas were separated into untreated, riboflavin solution-treated, and CXL-treated groups. The depth dependency of shear moduli within groups was assessed in femtosecond laser cut sheets. Dry weights were obtained for solids correction. RESULTS: In porcine full-thickness buttons and 300 µm anterior sheets, a significantly increased unidirectional transverse shear modulus was detected in riboflavin-treated and CXL-treated groups compared to the respective untreated groups. There was no significant difference in shear modulus between riboflavin- and CXL-treated groups. In all groups, the shear moduli were greater in the anterior sheets compared to posterior sheets. Similar results were detected in human corneas. CONCLUSIONS: A method for unidirectional transverse shear resistance measurement was developed. The shear moduli were greater in the anterior compared to the posterior sheets. Increase in shear moduli was observed in the riboflavin and CXL groups compared to the untreated group, indicating that the immediate effects of the riboflavin or CXL treatment may be due partly to ground substance/dextran-5-phosphate interaction.

Reduction of stromal swelling pressure after UVA-riboflavin cross-linking.

PURPOSE: We evaluated whether UVA-riboflavin collagen cross-linking (CXL) reduces stromal swelling pressure (SP) in porcine and human corneas ex vivo. METHODS: Porcine corneas (N = 35) were divided into five groups: Full-thickness buttons, riboflavin-treated buttons, CXL-treated buttons, riboflavin-treated anterior and posterior lamellae, and CXL-treated anterior and posterior lamellae. Riboflavin- or CXL-treated human corneas (n = 6) were cut into anterior and posterior lamellae. The force exerted by the specimens during swelling in saline was recorded and SP was calculated. Dry weights were obtained for solids correction. RESULTS: In full-thickness porcine buttons, a significantly reduced SP was observed after CXL (40.07 ± 3.86 mm Hg) compared to riboflavin treatment (68.13 ± 11.39 mm Hg, P = 0.02) at 5% compression. Also, a trend toward reduced SP in the CXL-treated anterior human lamellae (9.9 mm Hg) was found compared to the riboflavin group (25 mm Hg) at 5% compression. In the anterior porcine lamellae a significant SP reduction was observed in the CXL group versus the riboflavin group (P < 0.001, two-way ANOVA). Likewise, in the posterior porcine lamellae, a significant SP reduction was observed in the CXL group versus riboflavin alone (P < 0.05, two-way ANOVA). Posterior human lamellae did not differ in SP when comparing CXL and riboflavin groups. CONCLUSIONS: Our study demonstrated a significant reduction in anterior stromal SP in porcine and human corneas after CXL. This finding suggested that CXL may reduce corneal SP in vivo, and thereby reduce edema and improve vision. Thus, in the clinical setting, patients suffering from corneal edema may benefit from CXL treatment.

Inverse cutting of posterior lamellar corneal grafts by a femtosecond laser.

PURPOSE: Posterior lamellar grafting of the cornea has become the preferred technique for treatment of corneal endothelial dysfunction. Posterior lamellar grafts are usually cut by a micro-keratome or a femto-second laser after the epithelial side of the donor cornea has been applanated. This approach often results in variable central graft thickness in different grafts and an increase in graft thickness towards the periphery in every graft. The purpose of this study was to evaluate if posterior lamellar grafts can be prepared from the endothelial side by a femto-second laser, resulting in reproducible, thin grafts of even thickness. METHODS: A CZM 500 kHz Visumax femto-second laser was used. Organ cultured donor grafts were mounted in an artifical anterior chamber with the endothelial side up and out. Posterior grafts of 7.8 mm diameter and 130 micron thickness were prepared by femto-second laser cutting. A standard DSAEK procedure was performed in 10 patients with Fuchs endothelial dystrophy. Patients were followed-up regularly and evaluated by measurement of complications, visual acuity, corneal thickness (Pentacam HR), and endothelial cell density. RESULTS: Femto-laser cutting of grafts and surgery was uncomplicated. Rebubbling was necessary in 5 of 10 cases (normally only in 1 of 20 cases). All grafts were attached and cleared up during the first few weeks. After six months, the average visual acuity was 0.30 (range: 0.16 to 0.50), corneal thickness was 0.58 mm (range 0.51 to 0.63), and endothelial cell density was 1.570 per sq. mm (range: 1.400 to 2.000 cells per sq. mm). The grafts were of uniform thickness, but substantial interface haze was present in most grafts. CONCLUSIONS: Posterior lamellar corneal grafts can be prepared from the endothelial side using a femto-second laser. All grafts were clear after 6 months with satisfying endothelial cell counts. Poor visual acuity caused by interface scatter was observed in most patients. Femto-second laser cutting parameters needs to be optimised to enable smooth cutting in the posterior stroma.

Influence of suture regularity on corneal astigmatism after penetrating keratoplasty.

PURPOSE: To investigate whether suture regularity affects corneal astigmatism after keratoplasty. METHODS: Twenty-one patients undergoing penetrating keratoplasty for various corneal diseases were included in the study. The grafts were sutured in place using a single-running Nylon 10-0 suture, taking 24 bites. Immediately after surgery, standard calibrated images of the grafted eye were captured and stored. Using a dedicated image analysis programme, stitches and needle points were identified, and a number of suture regularity variables were calculated. Corneal topographic images were obtained before suture removal (12 months after surgery) and 3 months after suture removal (18 months after surgery). Topographic measures of astigmatism [surface regularity (SRI), surface asymmetry index (SAI) and simulated keratometric astigmatism] were calculated and correlated with the computed suture regularity variables. RESULTS: The average stitch length was 3.04 ± 0.28 mm and the distance between the outer needle points was 2.53 ± 0.09 mm. The SRI was 1.26 ± 0.36 and the SAI was 1.59 ± 0.67 after 12 months; these decreased to 1.03 ± 0.48 and 0.92 ± 0.46 after 18 months, respectively. Corneal astigmatism was 6.38 ± 2.99 and 5.87 ± 3.13 dioptres after 12 and 18 months, respectively. Suture regularity did not affect SAI, SRI or corneal astigmatism significantly 12 months after surgery. Eighteen months after surgery (3 months after suture removal), the standard deviation on the original stitch length was found to significantly increase corneal astigmatism. In addition, the size of the counter-clockwise angle between stitch and graft radian was correlated significantly with a lower SRI. CONCLUSION: The origin of corneal astigmatism after penetrating keratoplasty is multifaceted. Regular stitch length and stitch advancement on the surface appears to improve the optical quality of the graft after suture removal. Factors such as stitch depth, suture tension and variations in wound construction might also be important predictors of corneal astigmatism after penetrating keratoplasty.

Corneal distribution of riboflavin prior to collagen cross-linking.

PURPOSE: To evaluate the distribution of riboflavin in the corneal stroma, under varying concentrations and application time. MATERIALS AND METHODS: In 54 porcine eyes, the central corneal epithelium was removed, and 0.035, 0.1, or 0.2% riboflavin-5-phosphate (in 20% Dextran T-500) was applied for 10, 20, or 30 min (3 x 6 corneas in each of the 3 groups). Trephined corneal buttons were examined using confocal fluorescence microscopy. Stromal riboflavin distribution and concentration was determined by measuring riboflavin fluorescence in optical sections at 10 microm intervals through the entire cornea. The procedure was repeated in 7 human corneal donor grafts using 0.1% riboflavin-5-phosphate for 20 or 30 min. RESULTS: In porcine corneas, fluorescence intensity peaked within the first 50 microm followed by a steep decline to baseline. Increasing the riboflavin concentration from 0.1 to 0.2% did not increase stromal depth propagation, although a higher concentration in the anterior 200 microm was observed. Reducing the riboflavin application time from 30 to 20 min had no impact on corneal depth propagation or total riboflavin uptake. However, a 10-min further reduction of the application time caused a significantly reduced riboflavin uptake. In all human corneas, fluorescence peaked within the anterior 50 microm, followed by a steep decline to baseline over the next 200 microm; similar to the observations in porcine corneas. The human corneas imbibed more riboflavin compared to the porcine corneas. CONCLUSIONS: In human and porcine corneas, riboflavin does not appear to fully load the corneal stroma using the current clinical procedure. Instead, the uptake appears to be limited to the anterior approximately 200 microm. Changes in application time and riboflavin concentration have only little influence on stromal depth diffusion.

Riboflavin-UVA treatment in the management of edema and nonhealing ulcers of the cornea.

PURPOSE: Riboflavin-ultraviolet A (UVA) treatment induces cross-linking and stiffens the corneal stroma. A parallel reduction in stromal swelling and increased resistance to microbial and enzymatic degradation has been suggested. The purpose of this study was to evaluate the potential of riboflavin-UVA treatment in the management of corneal disorders, in particular edema due to endothelial decompensation and non-healing ulcers. METHODS: Two clinical series are reported, 11 eyes with endothelial decompensation and 14 eyes with non-healing ulcers. Treatment comprised a) abrasion of epithelium (if present), b) instillation of 0.1% riboflavin in saline, and c) irradiation at 365 nm UVA light over approximately 30 minutes (3 mW/cm(2)). Four eyes in the first group were treated twice. Postoperatively, all eyes were followed for at least 3 months. RESULTS: Reduction in corneal thickness was observed in 10 of 11 eyes with stromal edema and the majority also experienced improvement in vision. The effect occurred over weeks and lasted for months. Fourteen patients with non-healing ulceration were similarly treated; 6 healed, 8 showed no clear effect. CONCLUSIONS: In addition to the stiffening of keratoconic and ectatic cornea, riboflavin-UVA treatment is effective in reducing corneal edema and has the potential to heal corneal ulcers.